ArticleLeukemia2020
A novel BCMA PBD-ADC with ATM/ATR/WEE1 inhibitors or bortezomib induce synergistic lethality in multiple myeloma.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- The Efficacy and Safety of B-Cell Maturation Antigen (BCMA) Antibody-Drug Conjugates (ADC) in Development against Cancer: A Systematic Review.Oncology research · 2025Pooled it
- Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- High WEE1 expression is independently linked to poor survival in multiple myeloma.Blood cancer journal · 2025Article
- High WEE1 expression is independently linked to poor survival in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
- Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeted immunotherapy: harnessing the immune system to battle multiple myeloma.Cell death discovery · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Review
- Prostate cancer, chronic myelogenous leukemia and multiple myeloma in a single patient: a case report and review of the literature.Journal of medical case reports · 2023Review
- Studying the DNA damage response pathway in hematopoietic canine cancer cell lines, a necessary step for finding targets to generate new therapies to treat cancer in dogs.Frontiers in veterinary science · 2023Article
- Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?Cancers · 2022Review
- Targeting the DNA damage response beyond poly(ADP-ribose) polymerase inhibitors: novel agents and rational combinations.Current opinion in oncology · 2022Review
- Review
- γ-secretase inhibitors augment efficacy of BCMA-targeting bispecific antibodies against multiple myeloma cells without impairing T-cell activation and differentiation.Blood cancer journal · 2022Article
- IKZF1 selectively enhances homologous recombination repair by interacting with CtIP and USP7 in multiple myeloma.International journal of biological sciences · 2022Article
- Review
- Promising Antigens for the New Frontier of Targeted Immunotherapy in Multiple Myeloma.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
To target mechanisms critical for multiple myeloma (MM) plasma cell adaptations to genomic instabilities and further sustain MM cell killing, we here specifically trigger DNA damage response (DDR) in MM cells by a novel BCMA antibody-drug conjugate (ADC) delivering the DNA cross-linking PBD dimer tesirine, MEDI2228. MEDI2228, more effectively than its anti-tubulin MMAF-ADC homolog, induces cytotoxicity against MM cells regardless of drug resistance, BCMA levels, p53 status, and the protection conferred by bone marrow stromal cells and IL-6. Distinctly, prior to apoptosis, MEDI2228 activates DDRs in MM cells via phosphorylation of ATM/ATR kinases, CHK1/2, CDK1/2, and H2AX, associated with expression of DDR-related genes. Significantly, MEDI2228 synergizes with DDR inhibitors (DDRi s) targeting ATM/ATR/WEE1 checkpoints to induce MM cell lethality. Moreover, suboptimal doses of MEDI2228 and bortezomib (btz) synergistically trigger apoptosis of even drug-resistant MM cells partly via modulation of RAD51 and accumulation of impaired DNA. Such combination further induces superior in vivo efficacy than monotherapy via increased nuclear γH2AX-expressing foci, irreversible DNA damages, and tumor cell death, leading to significantly prolonged host survival. These results indicate leveraging MEDI2228 with DDRi s or btz as novel combination strategies, further supporting ongoing clinical development of MEDI2228 in patients with relapsed and refractory MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.